What treatments are recommended for low free testosterone and elevated Sex Hormone-Binding Globulin (SHBG)?

From the Guidelines

For low free testosterone with high sex hormone-binding globulin (SHBG), treatment typically involves testosterone replacement therapy (TRT) along with strategies to lower SHBG levels, as recommended by the most recent and highest quality study 1.

Treatment Options

• TRT options include:
  • Injectable testosterone cypionate or enanthate (100-200mg every 1-2 weeks)
  • Daily transdermal gels (50-100mg)
  • Testosterone pellets (implanted every 3-6 months)

Strategies to Lower SHBG Levels

• Dietary modifications:
  • Reducing fiber intake
  • Increasing protein consumption (1.2-1.6g/kg body weight daily)
  • Moderating carbohydrate intake
• Supplements:
  • Boron (6-10mg daily)
  • Magnesium (300-400mg daily)
  • Zinc (25-50mg daily)
  • Vitamin D (2000-5000 IU daily if deficient)

Lifestyle Changes

• Regular resistance training 3-4 times weekly
• Maintaining adequate sleep (7-9 hours nightly)
• Stress management
• Achieving a healthy body weight These approaches work because SHBG binds to testosterone, making it unavailable to tissues. By lowering SHBG through these interventions, more testosterone becomes bioavailable, potentially improving symptoms like fatigue, reduced muscle mass, decreased libido, and mood disturbances even without increasing total testosterone levels, as supported by studies 1.

From the FDA Drug Label

DOSAGE AND ADMINISTRATION Prior to initiating testosterone enanthate injection, confirm the diagnosis of hypogonadism by ensuring that serum testosterone concentrations have been measured in the morning on at least two separate days and that these serum testosterone concentrations are below the normal range Male hypogonadism: As replacement therapy, i.e., for eunuchism, the suggested dosage is 50 to 400 mg every 2 to 4 weeks.

The recommended treatment for low free testosterone and high SHBG is testosterone replacement therapy. The suggested dosage of testosterone enanthate injection is 50 to 400 mg every 2 to 4 weeks for male hypogonadism. 2

• The diagnosis of hypogonadism should be confirmed by measuring serum testosterone concentrations on at least two separate days.
• The dosage and duration of therapy will depend on the patient's response to treatment and appearance of adverse effects.
• Injections should be given slowly and deeply into the gluteal muscle. 2

From the Research

Treatment Options for Low Free Testosterone and High SHBG

• Testosterone replacement therapy (TRT) is a recommended treatment for hypogonadal men with low free testosterone levels 3, 4.
• The goal of TRT is to increase serum testosterone levels to a physiologic range, which can help alleviate symptoms such as decreased libido, erectile dysfunction, and depressed mood 4.
• There are various forms of TRT available, including buccal, nasal, subdermal, transdermal, and intramuscular (IM) routes of delivery 4.
• The choice of TRT depends on the patient's preference and medical history, and dose adjustment is possible with most delivery methods 3.

Effects of TRT on SHBG and Free Testosterone

• Studies have shown that TRT can decrease SHBG levels in hypogonadal men, which can lead to an increase in free testosterone levels 5, 6.
• However, the effects of TRT on SHBG and free testosterone can vary depending on the type of treatment and individual patient characteristics 5, 6.
• For example, one study found that testosterone enanthate treatment decreased SHBG levels in normal men and patients with Klinefelter's syndrome, while human chorionic gonadotropin (hCG) treatment had no effect on SHBG levels in hypogonadotropic hypogonadism patients 5.
• Another study found that oral testosterone undecanoate treatment decreased SHBG levels, while intramuscular injection of mixed testosterone esters and subcutaneous testosterone pellets had no significant effect on SHBG levels 6.

Identifying Clinical Subgroups for TRT

• Baseline SHBG levels and age may be used to identify clinical subgroups that respond differently to TRT 7.
• One study found that men with low baseline SHBG levels (≤28.1 nmol/L) and younger age (≤63 years) had a positive association between TRT and change in SHBG, while men with high baseline SHBG levels (>28.1 nmol/L) and older age (>63 years) had an inverse association 7.
• The study also found that TRT was associated with improvements in waist circumference, HbA1c, and International Index of Erectile Function (IIEF) score in certain subgroups, but not others 7.